Phenome-wide association study and precision medicine of cardiovascular diseases in the post-COVID-19 era.

SARS-CoV-2 infection causes injuries of not only the lungs but also the heart and endothelial cells in vasculature of multiple organs, and induces systemic inflammation and immune over-reactions, which makes COVID-19 a disease phenome that simultaneously affects multiple systems. Cardiovascular diseases (CVD) are intrinsic risk and causative factors for severe COVID-19 comorbidities and death. The wide-spread infection and reinfection of SARS-CoV-2 variants and the long-COVID may become a new common threat to human health and propose unprecedented impact on the risk factors, pathophysiology, and pharmacology of many diseases including CVD for a long time. COVID-19 has highlighted the urgent demand for precision medicine which needs new knowledge network to innovate disease taxonomy for more precise diagnosis, therapy, and prevention of disease. A deeper understanding of CVD in the setting of COVID-19 phenome requires a paradigm shift from the current phenotypic study that focuses on the virus or individual symptoms to phenomics of COVID-19 that addresses the inter-connectedness of clinical phenotypes, i.e., clinical phenome. Here, we summarize the CVD manifestations in the full clinical spectrum of COVID-19, and the phenome-wide association study of CVD interrelated to COVID-19. We discuss the underlying biology for CVD in the COVID-19 phenome and the concept of precision medicine with new phenomic taxonomy that addresses the overall pathophysiological responses of the body to the SARS-CoV-2 infection. We also briefly discuss the unique taxonomy of disease as Zheng-hou patterns in traditional Chinese medicine, and their potential implications in precision medicine of CVD in the post-COVID-19 era.

Partitioning of evapotranspiration and the influencing factors of evapotranspiration components in a shrub ecosystem dominated by Artemisia ordosica and Hedysarum fruticosum var. mongolicum in the Mu Us Desert, Northwest China.

Evapotranspiration (ET) is an important part of water cycle and energy flow in ecosystem. Accurate estimation of ET and its components is critical for understanding the impacts of ecophysiological processes on ecosystem water balance and plant water use strategy. Using the eddy-covariance technique and the micro-lysimeter, we measured ET, evaporation (E), transpiration (T) of the Artemisia ordosica-Hedysarum fruticosum var. mongolicum shrubland in the Mu Us Desert during May 20 to September 15, 2019, quantified the ET components, and analyzed the seasonal characteristics and influencing factors of ET and its components. The results showed that T was the main component of ET in the growing season, with a T/ET of 53.1%. T/ET increased and E/ET decreased as precipitation decreased. The partitioning of evapotranspiration was regulated by precipi-tation. At the seasonal scale, the value of E was positively correlated with soil water content at 10 cm depth (SWC10) and net radiation (Rn), while SWC10 was the main factor influencing E. The value of T increased with the increases of Rn and leaf area index (LAI), and increased first and then decreased with the increases of soil water content at 30 cm layer (SWC30). T was affected by SWC30, Rn and LAI. Moisture was the main influencing factor of ET. The ET/P in the growing season was 109.2% and was 250.5% in May, indicating that the water consumption of ET in early growing season was partly from the precipitation in non-growing season.

[Effects of wine processed Rheum palmatum on tissue distribution of aloe-emodin, rhein and emodin in rats].

Under the traditional processing theory "wine processing could promote the efficacy", Rhubarb after wine processing could treat the upper energizer diseases such as red swelling, and breath sores. Processing changes the medicinal properties of rhubarb, and thus results in different focuses in clinical application. In this study, a sensitive and specific method was developed for the determination of aloe-emodin, rhein and emodin in rats tissue. Rhubarb raw materials and its wine processed decoction were given to SD rats respectively by gavage administration, and then the contents of aloe-emodin, rhein and emodin in the tissues (heart, lung, brain, liver, kidney) were determined by HPLC-MS to explore the effect of wine processing on free anthraquinones in rat tissues. Experimental results showed that wine processing can significantly change the distribution of aloe emodin, rhein and emodin in rats in vivo, and the distribution of these components was increased in heart and lung tissues.There was no significant change of distribution in the liver and the kidney as compared with raw product group, and these three ingredients were not detected in the brain, indicating that aloe-emodin, rhein, emodin can not pass through the blood brain barrier.Therefore, wine processing had greater effect on distribution of free anthraquinones in rat tissues.This also verified the theory of traditional Chinese medicine, providing experimental basis for rhubarb processing mechanism.

Diallyl trisulfide suppresses tumor growth through the attenuation of Nrf2/Akt and activation of p38/JNK and potentiates cisplatin efficacy in gastric cancer treatment.

Diallyl trisulfide (DATS), a garlic organosulfide, has shown excellent chemopreventive potential. Cisplatin (DDP) is widely used to treat solid malignant tumors, but causing serious side effects. In the current study, we attempted to elucidate the chemopreventive mechanisms of DATS in human gastric cancer BGC-823 cells in vitro, and to investigate whether DATS could enhance the anti-tumor efficacy of DDP and improve quality of life in BGC-823 xenograft mice in vivo. Treatment with DATS (25-400 µmol/L) dose-dependently inhibited the viability of BGC-823 cells in vitro with an IC50 of 115.2±4.3 µmol/L after 24 h drug exposure. DATS (50-200 µmol/L) induced cell cycle arrest at G2/M phase in BGC-823 cells, which correlated with significant accumulation of cyclin A2 and B1. DATS also induced BGC-823 cell apoptosis, which was accompanied by the modulation of Bcl-2 family members and caspase cascade activation. In BGC-823 xenograft mice, administration of DATS (20-40 mg·kg-1·d-1, ip) dose-dependently inhibited tumor growth and markedly reduced the number of Ki-67 positive cells in tumors. Interestingly, combined administration of DATS (30 mg·kg-1·d-1, ip) with DDP (5 mg/kg, every 5 d, ip) exhibited enhanced anti-tumor activity with fewer side effects. We showed that treatment of BGC-823 cells with DATS in vitro and in vivo significantly activated kinases such as p38 and JNK/MAPK and attenuated the Nrf2/Akt pathway. This study provides evidence that DATS exerts anticancer effects and enhances the antitumor efficacy of DDP, making it a novel candidate for adjuvant therapy for gastric cancer.

Insight into the short- and long-term effects of Cu(II) on denitrifying biogranules.

This study aimed to investigate the short- and long-term effects of Cu(2+) on the activity and performance of denitrifying bacteria. The short-term effects of various concentrations of Cu(2+) on the denitrifying bacteria were evaluated using batch assays. The specific denitrifying activity (SDA) decreased from 14.3 ± 2.2 (without Cu(2+)) to 6.1 ± 0.1 mg N h(-1)g(-1) VSS (100 mg Cu(2+)L(-1)) when Cu(2+) increased from 0 to 100 mg L(-1) with an increment of 10 mg Cu(2+)L(-1). A non-competitive inhibition model was used to calculate the 50% inhibition concentration (IC50) of Cu(2+) on denitrifying sludge (30.6 ± 2.5 mg L(-1)). Monod and Luong models were applied to investigate the influence of the initial substrate concentration, and the results suggested that the maximum substrate removal rate would be reduced with Cu(2+) supplementation. Pre-exposure to Cu(2+) could lead to an 18.2-46.2% decrease in the SDA and decreasing percentage of the SDA increased with both exposure time and concentration. In the continuous-flow test, Cu(2+) concentration varied from 1 to 75 mg L(-1); however, no clear deterioration was observed in the reactor, and the reactor was kept stable, with the total nitrogen removal efficiency and total organic carbon efficiency greater than 89.0 and 85.0%, respectively. The results demonstrated the short-term inhibition of Cu(2+) upon denitrification, and no notable adversity was observed during the continuous-flow test after long-term acclimation.